Valproic acid and sodium valproate are drugs useful for the treatment of epileptic seizures or convulsions.
Valproic acid has molecular formula C.sub.8 H.sub.16 O.sub.2 and molecular weight 144.21. It is a liquid at room temperature (20.degree. C. to 30.degree. C.) and thus is not suitable for manufacture of solid pharmaceutical dosage forms such as tablets for oral administration.
Sodium valproate is the sodium salt of valproic acid. It has molecular formula C.sub.8 H.sub.15 O.sub.2 N.sub.a and molecular weight 166.19. It is a solid at room temperature and does not melt even at substantially higher temperatures. It is thus more suitable than valproic acid for manufacture of solid dosage forms. However, sodium valproate is highly hygroscopic and readily absorbs water from the atmosphere, which leads to problems of poor stability of compositions made from sodium valproate.
It is thus desirable to have a material that combines certain properties of sodium valproate with certain properties of valproic acid. That is to say, it is desirable to have a substance with the therapeutic properties of valproic acid or sodium valproate which, like sodium valproate, is a solid at room temperature but, like valproic acid, is non-hygroscopic.
U.S. Pat. No. 5,212,326 describe such a substance. It is described as being an oligomer having at 1:1 molar ratio of sodium valproate and valproic acid. That substance is now known by the name divalproex sodium.
According to U.S. Pat. No. 5,212,326, divalproex sodium is made by dissolving one mole each of valproic acid and sodium valproate in acetone and cooling the solution to O.degree. C. to precipitate the compound. Alternately, it is made by adding one mole of sodium hydroxide dissolved in an acetone-miscible solvent to two moles of valproic acid dissolved in acetone and evaporating the solvents.
As described in U.S. Pat. No. 5,212,326, this new compound, divalproex sodium, represents a new single chemical molecule.
Divalproex sodium has molecular formula C.sub.16 H.sub.31 O.sub.4 N.sub.a and molecular weight 310.4. The molecular formula is the sum of the molecular formulas of valproic acid and sodium valproate, and similarly the molecular weight is the sum of the two molecular weights. It has a melting point of about 100.degree. C.
While divalproex sodium as disclosed in U.S. Pat. No. 5,212,326 has the desired features of being a nonhygroscopic solid, it has the disadvantage of requiring the use of acetone or other organic solvents to prepare it from valproic acid and sodium valproate or sodium hydroxide.
The organic solvents are expensive and also give rise to concerns about toxic effects on production personnel and environmental concerns relating to disposal of the solvent.
It is thus the object of the present invention to enable production of a substance that is functionally equivalent to divalproex sodium as disclosed in U.S. Pat. No. 5212316, in that it is a nonhygroscopic solid, but that can be made from valproic acid and sodium valproate without use of organic solvents.